Epigenomics refers to the inheritance of information based on gene expression levels that do not entail changes in DNA sequence, as opposed to genetics which refers to information transmitted on the basis of gene sequence. The best understood epigenomic marks include DNA methylation, histone modifications, and micro-RNA (miRNA). Epigenomics has been called the science of change. It is a biological endpoint for endogenous and exogenous factors that determine health and disease.
DNA methylation is one of the most common alterations in human neoplasia, including breast cancer. DNA methylation refers to the addition of a methyl group to the cytosine ring of those cytosines that precede guanosine (CpG dinucleosides) to form methyl cytosine. Detection of changes in DNA methylation may offer an alternative to screening and may offer data for long-term management of women treated for breast cancer.
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver in adults, the fifth most common solid tumor, and the third most common cause of cancer death worldwide. HCC incidence and death rates are steadily rising in the United States and demonstrate the highest average annual percent increase of the top 15 cancers by incidence. HCC patients, and people at risk of developing HCC, have profound unmet medical and public health needs. Advances in HCC treatment such as, liver transplantation, surgical resection, and loco regional therapies have only impacted a fraction of the population at risk. More than 70% of HCC patients present with advanced disease and will not benefit from these treatment modalities, or from the sole chemotherapeutic agent approved for advanced HCC patients.
Most HCC patients cannot benefit from current treatment modalities because they are diagnosed with advance disease. The obesity epidemic and the increase in HCV related cirrhosis will eventually lead to an increase in the incidence of HCC. The projected increase in HCC incidence creates an urgent need for translational research that leads to novel screening and clinical management for HCC. HCC mortality, however, can be decreased by effective early detection strategies followed by curative treatment such as resection, liver transplantation, or liver ablation. The smaller the HCC tumor is at diagnosis, the higher the likelihood of therapeutic success. Consequently, the goal of screening programs for at risk populations is to detect and treat HCC at an early stage and, specifically, when tumors can be detected before they have grown larger than 2 cm in diameter.
According to American Association for the Study of Liver Diseases (AASLD) guidelines, HCC screening should be done with ultrasound every 6-12 months. HCC diagnosis requires a specific algorithm with dynamic imaging techniques for the characterization of liver nodules detected during surveillance of patients with cirrhosis with ultrasound (US). A combination of dynamic contrast imaging techniques, contrast-enhanced ultrasound (CE-US), computed tomography (CT), and gadolinium magnetic resonance imaging (MRI), are considered the standard of care for the radiological diagnosis of HCC in cirrhotic patients. However, the accuracy of radiological diagnosis depends largely on the degree of arterial hypervascularization, which increases with tumor size, and also by cell grading of the nodule. HCC diagnostic accuracy could be improved if a molecular biomarker was identified that could distinguish HCC from non-HCC cells in the nodule.
Similar to HCC, gastric cancer (GC) is the fourth most common cancer in both sexes and the second cause of cancer-related death around the world. The prognosis of GC is closely related to the stage of disease at the time of diagnosis. Early GC is defined as cancer confined to the mucosa or submucosa regardless of the presence of lymph node metastasis. Apart from conventional, magnifying narrow-band imaging (NBI), endoscopy has been recently introduced for the diagnosis of early GC. However, missed diagnoses of GC on endoscopy are still common, with false-negative rates ranging from 5 to 19%. Whereas the five year survival rate for early GC is greater than 90%, prognosis for advanced GC is still poor. A contributing factor to this poor prognostication rate is the difficulty in distinguishing early GC from benign peptic ulcer or gastritis in the ambulatory setting, as most of the patients with early GC do not have specific symptoms. Due to the above mentioned reasons, less than 20% of GCs are diagnosed at an early stage in several countries.
The integration of epigenomics and DNA methylation to clinical and population based studies is still lacking. As such, there still exists a need for better clinical methods for determining biomarkers useful in detection and diagnosis of hepatic and gastric cancers.